Optimal adherence to TNF inhibitors for rheumatoid arthritis may be 60% of days covered
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Key takeaways:
- Adherence to TNF inhibitors for rheumatoid arthritis was associated with lower risk for oral glucocorticoid use and hospitalization.
- The optimal adherence threshold may be a proportion of days covered of approximately 60%.
Greater adherence to TNF inhibitor therapy for rheumatoid arthritis led to fewer adverse events, with the optimal adherence threshold being approximately 60% of days covered, according to data published in Clinical Rheumatology.
“Currently, the [medication possession ratio of 80%] adherence threshold is used to dichotomize patients into adherent and non-adherent groups,” Jennifer Toth Harris, PharmD, PhD, a graduate student at the University of Mississippi during the study, and colleagues wrote. “This threshold was initially supported by Haynes et al., who found that patients who used at least 80% of their antihypertensive medications for 6 months had significantly lower diastolic blood pressure.
“The 80% threshold for adherence has become the norm in RA studies, cited as the value typically used,” they added. “Although the 80% threshold is normally used to categorize patients as adherent and non-adherent, the determination of this threshold in RA patients using RA-related outcomes has not been published.”
To determine an evidence-based optimal adherence threshold for TNF inhibitors in patients with RA, Toth Harris and colleagues conducted a study of the 5% Medicare national sample of administrative claims from 2012 to 2018. Their analysis included 1,190 patients with RA (mean age, 61.3 years) who initiated a TNF inhibitor from July 2012 through December 2017.
Medication adherence was calculated using the proportion of days covered.
“Because medication adherence changes over time, [proportion of days covered (PDC)] was estimated as a time-varying variable for each day of the follow-up period, based on medication fill behavior in the previous 90 days,” the researchers wrote.
Cox regression was used to evaluate the time to use for oral and injected glucocorticoids, as well as hospitalizations, ED visits, serious infections, and all of the above taken together as a composite.
According to the researchers, nearly three-quarters of the patients (n = 865) demonstrated at least one of those outcomes. A 10% bump in PDC was significantly associated with a decreased risk for the composite outcome (HR = 0.98; 95% CI, 0.96-1), use of oral glucocorticoids (HR = 0.93; 95% CI, 0.91-0.96) and hospitalization (HR = 0.96; 95% CI, 0.94-0.99). However, it was also associated with an increased risk for ED visits (HR = 1.04; 95% CI, 1.01-1.07).
The researchers wrote that they calculated an optimal proportion-of-days-covered threshold of approximately 60%, based on incident/dynamic time-dependent receiver operating characteristic curves and Youden’s J index.
The optimal PDC thresholds were 0.64 (adjusted HR = 0.86; 95% CI, 0.73-1) for the composite outcome, 0.59 (HR = 0.57; 95% CI, 0.47-0.7) for oral glucocorticoid use, and 0.56 (HR = 0.7; 95% CI, 0.57-0.86) for hospitalization. According to the researchers, the area-under-the-curve for all of these were between 0.5 to 0.6 and “all significantly greater than 0.5.”
“The average 90-day PDC of self-injectable TNF inhibitors in Medicare patients with RA initially starts above 80% but then decreases to about 60% after 1 year,” Toth Harris and colleagues wrote. “Higher PDC was associated with a reduced risk of hospitalization, oral GC use, and the composite outcome.
“The optimal PDC threshold for TNF inhibitors in RA was found to be around 60% at 365 days,” they added. “More research is needed to determine the optimal adherence threshold in DMARD therapy for RA over different time intervals and at various time points after the index date than the 90-day intervals and 365 days of follow-up used in this study.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
In rheumatology, adherence to prescribed medications is often an issue. The prevalence of clinically undetected partial adherence, or nonadherence, to prescribed medications is greater than we often realize. Michelle Petri, MD, MPH, and colleagues performed a previous study of patients prescribed hydroxychloroquine for lupus and found that a number of them who were seen routinely, verbalized adherence to the treatment regimen, and were compliant with eye examinations, were not taking hydroxychloroquine.
We have major adherence problems with osteoporosis medications. It is an asymptomatic disease, and our dental colleagues disparage patients from taking osteoporosis medications for fear of osteonecrosis of the jaw (ONJ). They even encourage them to stop anabolic medications such as teriparatide or abaloparatide that may actually help ONJ.
Measurement of adherence is not easy. At our clinic visits, we reconcile the medication list, but verbal histories have been found to be inaccurate, as noted by Dr. Petri’s study.
Adherence is also a major concern in clinical trials. Both the positive and negative effects of the study medication depend on the subjects reliably taking it. This nonadherence can lead to erroneous adverse events or lack of benefit. Due to this issue, electronic means of monitoring compliance have been introduced and found to be superior to history taking or pill counts. Still, this has not been introduced into clinical practice in any meaningful way. Measuring blood levels is available for some medications, providing us with a picture of just one point in time.
Adherence and persistence are not new in medicine and will continue to be an issue due to human nature.
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